Palladium anchored to BisPyP@bilayer-SiO2@NMP organic–inorganic hybrid as an efficient and recoverable novel nanocatalyst in suzuki and stille C–C coupling reactions

The palladium anchored to BisPyP@bilayer-SiO2@NMP organic–inorganic hybrid was employed as an effective and recyclable organometallic catalyst in Suzuki and Stille C–C coupling reactions. The structure of this magnetic nanocatalyst was determined using various techniques such as SEM, TEM, FT-IR, EDS, ICP-OES, VSM, N2 adsorption–desorption isotherms, XRD, and TGA. In both of the mentioned coupling paths, the yields of the products were very favorable and ranged from 90 to 98%. Also, they had significant features compared to previous reports, such as very short reaction time (5–15 and 7–20 min respectively in the Suzuki and Stille reactions), easy work-up, broad substrate scope, ease of separation of the catalyst using a magnet, suitable reproducibility of the catalyst in 6 runs, heterogeneous nature of the catalyst and not washing it during consecutive runs with confirmation of hot filtration and ICP-OES methods.


Preparation of the catalyst
In order to produce the Pd-BisPyP@bilayer-SiO 2 @NMP catalyst, we first created Fe 3 O 4 magnetic nanoparticles using the co-precipitation approach and intermediate I (xSiO 2 @Fe 3 O 4 ) according to prior research 51 .In continuation, in order to synthesize Fe 3 O 4 coated with two layers of silica (bilayer-SiO 2 @Fe 3 O 4 ), intermediate I (0.1 g) was dispersed in a mixed solution of deionized water (80 mL), cetyltrimethylammonium bromide (CTAB, 0.3 g), aqueous ammonia (25 wt%, 1 mL), and ethanol (60 mL) via ultrasonication (25 min).The next step was to mix a suspension containing 0.2 g of intermediate II, 1.66 mM of 3-chloropropyltriethoxysilane, and 25 mL of dry toluene solvent under reflux for 24 h.After the end of the reflux time to produce intermediate III, the resulting precipitate was filtered and washed with ethanol, toluene and deionized water.The 1,3-bis(4-pyridyl)propane was then immobilized on its surface by stirring a combination of 1,3-bis(4-pyridyl)propane (0.1 g), intermediate III (0.3 g), and toluene (25 mL) for 14 h while it was refluxed in an N 2 gas atmosphere (Intermediate IV).The final stage involved dispersing Intermediate IV (0.5 g) in ethanol and combining it with 0.25 g of palladium acetate that refluxed for 24 h.After that, the NaBH 4 (0.4 mmol) was added to the reaction mixture and stirred for 3 h.The black solid product Pd-BisPyP@bilayer-SiO 2 @NMP was obtained by filtration, washed with ethanol and dried in oven at 70 °C (Scheme 1).

Results and discussion
The successful functionalization of the bare Fe 3 O 4 nanoparticles can be deduced from the FT-IR technique.The FT-IR spectra for NMP (Fe 3 O 4 ) (i), bilayer-SiO 2 @NMP (ii), BisPyP@bilayer-SiO 2 @NMP (iii), and Pd-BisPyP@ bilayer-SiO 2 @NMP (4), are demonstrated in Fig. 1.In Fig. 1 i, the two peaks at 463 and 574 cm −1 are attributed to the vibrations of Fe-O bond 52 .In the FT-IR pattern of bilayer-SiO 2 @NMP, the coating of bare Fe 3 O 4 nanoparticles with silica layers was confirmed by observing the absorption band related to Si-O-Fe vibration at 950 cm −152 .Also, the 803 and 1026 cm −1 bands are corresponded to the symmetric and asymmetric vibrations of Si-O-Si in SiO 2 (Fig. 1ii) 52 .In Fig. 1iii, the presence of immobilized 3-chloropropyltriethoxysilane (nPr-Cl@ bilayer-SiO 2 @NMP), and the grafting 1,3-bis(4-pyridyl)propane to intermediate III are confirmed via Si-C stretching vibration at 1045 cm −153 , and C-N stretching vibration at 1380 cm −1 , respectively 53 .Additionally, the anchoring of palladium to BisPyP@bilayer-SiO 2 @NMP was confirmed with a shift of C=N vibration stretching in Pd-BisPyP@bilayer-SiO 2 @NMP (1660 cm −1 in Fig. 1iv), compared to BisPyP@bilayer-SiO 2 @NMP (1670 cm −1 in Fig. 1iii), to a lower frequency which is the reason for this shift is the coordination of Pd to supported BisPyP onto functionalized bilayer-SiO 2 @NMP 21 .Other adsorptions in the structure of the catalyst are mentioned in Table 1.
SEM was used to analyze the surface morphology of the Pd-BisPyP@bilayer-SiO 2 @NMP nanocatalyst.Quasispherical particles with an average size of 15 to 60 nm can be seen in the SEM image of Pd-BisPyP@bilayer-SiO 2 @ NMP (Fig. 2).
The study of the TEM images of BisPyP@bilayer-SiO 2 @NMP (a), and Pd-BisPyP@bilayer-SiO 2 @NMP (b) depicted in Fig. 3 amply supports the conclusions drawn from the SEM image, because the quasi-spherical shape of the nanoparticles can be clearly seen in these images.In addition, the comparison of these two images shows that the quasi-spherical structure of the substrate nanoparticles has not undergone much change after anchoring palladium on it.
In another study, the structure of the catalyst was reviewed with a high-resolution TEM image (Fig. 4).This image supports the distribution of Pd particles throughout the support, which can be seen as black dots.Scheme 1.The synthesis steps Pd-BisPyP@bilayer-SiO 2 @NMP.
Table 1.FT-IR data of NMP (Fe 3 O 4 ) (i), bilayer-SiO 2 @NMP (ii), BisPyP@bilayer-SiO 2 @NMP (iii), and Pd-BisPyP@bilayer-SiO 2 @NMP (iv).Energy dispersive X-ray spectroscopy analysis, often called EDS, is a practical technique for revealing information on different catalyst elements.Figure 5 confirms the successful fabrication of nanoparticles by showing the presence of C, O, N, Fe, Si, Cl and Pd species in the Pd-BisPyP@bilayer-SiO 2 @NMP nanocatalyst structure.Meanwhile, the elemental mapping technique images support the presence of all the mentioned constituent elements in the mesoporous skeleton (Fig. 6).It is worth noting, using inductively coupled plasma atomic emission spectroscopy, the precise quantity of palladium in Pd-BisPyP@bilayer-SiO 2 @NMP was determined to be 2.123 × 10 -3 mol g −1 .
Magnetic measurement for bare Fe 3 O 4 (a) and Pd-BisPyP@bilayer-SiO 2 @NMP (b) were carried out, and results are demonstrated in Fig. 7.According to this figure, the saturation magnetic value of catalyst (44.61 emu g −1 ) is lower than bare Fe 3 O 4 (73.84 emu g −1 ).This difference could be attributed to the presence of silica layers and the Pd-BisPyP complex attached to the nanoparticle surface.However, by applying an external magnetic field, the catalyst can be rapidly separated from the reaction mixture.
Investigating the porosity of the Pd-BisPyP@bilayer-SiO 2 @NMP nanocatalyst and its generating components was done using the nitrogen adsorption-desorption technique (Fig. 8).In Table 2, the findings of this  investigation are enumerated.According to the information in this table, Pd-BisPyP@bilayer-SiO 2 @NMP has a lower specific surface area than BisPyP@bilayer-SiO 2 @NMP, xSiO 2 @Fe 3 O 4 , and Fe 3 O 4 ; this is because organic groups and Pd complexes have been anchored on the mesoporous channels of magnetic silica nanoparticles.In addition, the pore size distribution (BJH model) and BET curves of the catalyst are provided in the supplementary material (Figs.S7 and S8, respectively).
Thermal gravimetric analysis (TGA) was used to infer the thermal stability of the produced nanocatalyst and the formation of bonds between the complex and the nanoparticles.Figure 9 displays the TGA curves for bare NMP (green curve), bilayer-SiO 2 @NMP (blue curve), and the Pd-BisPyP@bilayer-SiO 2 @NMP (red curve).The TGA diagram of all three samples shows a slight weight loss below 200 °C, which is caused by the removal of surface hydroxyl groups and physically absorbed solvents.The TGA curve of Pd-BisPyP@bilayer-SiO 2 @NMP showed two other stages of weight loss in addition to the preliminary weight loss (3.09% weight loss at temperature below 200 °C): (i) 10.72% weight loss in the temperature range of 200-380 °C (arising from decomposition of organic moieties of the complex), and (ii) 9.83% decrease weight between 380 and 700 °C (due to the decomposition of silanol groups) 54 .The above observations confirmed the thermal stability of the catalyst and the immobilization of the palladium complex on the bilayer-SiO 2 @NMP.Table 2. Texture properties of Pd-BisPyP@bilayer-SiO 2 @NMP.a r p,peak : Mean pore radius.www.nature.com/scientificreports/ The structural characteristics of bare NMP (crimson pattern), and Pd-BisPyP@bilayer-SiO 2 @NMP (blue pattern) were investigated using the XRD method in Fig. 10.The XRD pattern of these two samples, which consists of many peaks at 2θ = 30.66°(220), 34.50° (311), 43.33° (400), 52.66° (422), 56.11° (511) and 62.02° (440), which are related to the crystallographic faces of Fe 3 O 4 particles 55 .Furthermore, the existence of Pd in the catalyst structure was confirmed by the Bragg angles at = 40.01°(111), 46.29° (200), and 68.01° (220) (blue pattern) 56 .It is worth noting that the broad peak at 2θ = 20-30°, and also the peaks observed at 2θ = 18.01°, 48.65°, 49.33°, 37.33° and 38.41° indicate the presence of amorphous silica around the Fe 3 O 4 particles and the crystalline nature of the catalyst, respectively 54 .

Examine of the catalytic property
The catalytic performance of Pd-BisPyP@bilayer-SiO 2 @NMP in the C-C cross-coupling reaction of aryl halides with phenylboronic acid and triphenyltin chloride was carefully studied.In this regard, to determine the optimize conditions, the reaction between iodobenzene and phenylboronic acid was chosen as a model, and the effect of various factors, including temperature, amount of catalyst, solvent, and base on it was monitored.The results are shown in Table 3.In the first step, the effect of the nature of the solvent on the reaction of the model was studied.The results showed that the type of solvent used has a significant impact on the progress of the reaction, so that no product was observed in 1,4-dioxane (Table 3, entry 1), and small amounts of the product were obtained in H 2 O and EtOH in the presence of 5 mg of catalyst (Table 3, entries 2 and 3).However, in solvents such as DMF (dimethylformamide) and DMSO (dimethyl sulfoxide), the corresponding biphenyl product was isolated with 69 and 72 yields, respectively (Table 3, entries 4 and 5), and the highest yield was observed in PEG-400 solvent (Table 3, entry 6).Therefore, the PEG-400 solvent was chosen as the most suitable solvent for the mentioned reaction.In the second step, we studied the effect of different bases on the model's reaction.These bases included organic bases (DMAP, Et 3 N), monobasic (KOH, NaOH), dibasic (Na 2 CO 3 ), and NaHCO 3 (Table 3, entries 6-11).The results showed that Na 2 CO 3 can be a highly effective base for the Suzuki cross-coupling reaction (Table 3, entry 6).Also, KOH and NaOH, despite being stronger bases than Na 2 CO 3 based on their known K b values, ultimately did not lead to a significant yield of the product, because according to the studies of Knecht and his colleagues 57 , for monobasic systems (KOH, NaOH), the amount of free and active hydroxide compared to Na 2 CO 3 and NaHCO 3 is more, and this causes their strong combination with palladium species and decrease in biphenyl efficiency for cross-coupling reaction.Also, the reason for the ineffectiveness of organic bases such as Et 3 N and DMAP is their weak play power.The result of this study, as well as the failure to perform the reaction in the absence of base (Table 3, entry 12), proved that an average basic capacity is necessary to carry out the mentioned reaction using Pd-BisPyP@bilayer-SiO 2 @NMP.In the third step, our studies were focused on the effect of temperature on the progress of the reaction (Table 3, entries 6 and 13-15).Examining the result of the model reaction in the temperature range of 25 to 90 °C reflected the fact that the reaction is sensitive to temperature, so that a higher temperature can shorten the reaction time and cause a better progress of the reaction.Further investigations showed that the best temperature for the reaction progress is 70 °C (Table 3, entry 6).In the fourth step, the impact of the amount of phenylboronic acid on the performance was also studied (Fig. 11).The reactions performed in the presence of 0.7, 0.8, 0.9, and 1.0 mmol of phenylboronic acid provide 61, 79, 86, Figure 10.XRD patterns of bare NMP (crimson pattern), and Pd-BisPyP@bilayer-SiO 2 @NMP (blue pattern).www.nature.com/scientificreports/and 98 isolated yields, respectively.It has been determined that 1 mmol of phenylboronic acid with 1 mmol of iodobenzene are the optimal amounts to complete the reaction.In the last step, the model reaction was checked with quantities of 4, 5 and 6 mg of Pd-BisPyP@bilayer-SiO 2 @NMP because the coupling reaction does not occur under catalyst-free conditions (Table 3, entry 18).It was found that 5 mg of BisPyP@bilayer-SiO 2 @NMP is the optimal amount (Table 3, entry 6), while reducing the amount of catalyst to 4 mg in 60 min resulted in lower efficiency (Table 3, entry 16), increasing the amount of its catalyst to 6 mg did not show superiority over the optimal state (Table 3, entry 17).After determining the best conditions for the coupling of iodobenzene with phenylboronic acid, in another study this reaction was carried out in the presence of the catalyst parents, i.e.NMP (Fe 3 O 4 ) (Table 4, entry 1), bilayer-SiO 2 @NMP (Table 4, entry 2), BisPyP@bilayer-SiO 2 @NMP (Table 4, entry 3), and also Pd-BisPyP@ xSiO 2 @NMP (The only difference of this catalyst compared to Pd-BisPyP@bilayer-SiO 2 @NMP is the use of a silica layer (not two layers) around Fe 3 O 4 ) (Table 4, entry 4).Subsequently, the amount of palladium in the Pd-BisPyP@bilayer-SiO 2 @NMP and Pd-BisPyP@xSiO 2 @NMP measured via the ICP technique, which was equal to 2.123 × 10 −3 and 1.112 × 10 −3 mol g −1 , respectively.Experimental evidence from the ICP technique and Table 4 demonstrated that trick of utilizing two layers of SiO 2 on NMP, and also anchoring palladium on the BisPyP@ bilayer-SiO 2 @NMP was effective for the better progress of the reaction, because the reaction failed in the presence of the catalyst's parents (Table 4, entries 1-3), and only when they connect to each other and form the catalyst, a strong synergistic effect of the catalyst is observed.Immobilization of two layers of SiO 2 on NMP leads to the bonding of organic groups to the surface of the substrate, and this causes more palladium to enter the mesoporous channels, and complete the reaction with less amount of catalyst.Besides, the use of double-layer silica prevents the aggregation of magnetic nanoparticles.
To find out the scope of the catalytic system under examination, cross-coupling of phenylboronic acid with diverse aryl halides was tested.The results showed that all reactions proceed at high speed to obtain the corresponding biphenyl derivative with excellent efficiency (Table 5).The electron-donating or electron-withdrawing properties of the substituents do not seem to have a significant effect on the product yield.Also, Aryl bromides and aryl iodides provide better results than aryl chlorides.
For the Stille reaction, the Pd-BisPyP@bilayer-SiO 2 @NMP catalyst also displays a high activity in PEG-400 solvent through 0.5 mmol of triphenyltin chloride (Ph 3 SnCl).As the data in Table 6 reflect, the results are similar to those related to the Suzuki reaction.
To demonstrate the selectivity of our catalyst in both Suzuki and Stille coupling methods, 1-bromo-4-chorobenzene was coupled with PhB(OH) 2 and Ph 3 SnCl (Table 5 Entry 15 and Table 6 Entry 10, respectively).The results showed that the coupling occurs only with the bromo functional group, meaning the chloro functional group remains intact during both cross-coupling reactions (Scheme 2).
Scheme 3 shows the catalytic cycle of the Suzuki reaction in the presence of Pd-BisPyP@bilayer-SiO 2 @NMP catalyst in the following 3 steps, which is supported by the literature 65 : (1) the oxidative addition of Pd to Ar-X (aryl halide), and formation of organopalladium VI in the vicinity of Na 2 CO 3 (2) the transmetallation of VI gives intermediate VII in the presence of phenylboronic acid, and finally (3) product formation and regeneration of palladium catalyst (V) by reductive elimination of intermediate VII.

Reusability of catalyst
It is critical to recover and reuse catalysts in green catalytic processes for economic and environmental reasons.As a consequence, the reusability of Pd-BisPyP@bilayer-SiO 2 @NMP was investigated in the coupling of iodobenzene with phenylboronic acid, and the findings are shown in Fig. 12.After the completion of the reaction, the catalyst was separated using an external magnet and washed with ethyl acetate to extract the product for this investigation.The recovered catalyst was reused up to six times without losing substantial catalytic activity.The average isolated yield for six consecutive cycles is 96%, indicating that this catalyst is recyclable.

Catalyst leaching study
ICP-OES and hot filtration tests were used to investigate palladium leaching from Pd-BisPyP@bilayer-SiO 2 @ NMP.The quantity of palladium in the fresh and reused catalysts was 2.123 × 10 -3 mol g −1 and 2.109 × 10 -3 mol g −1 , respectively, according to ICP-OES analysis, indicating that palladium leaching of this catalyst is insignificant.A hot filtration test for the coupling of iodobenzene with phenylboronic acid was explored to assess the stability and heterogeneous nature of Pd-BisPyP@bilayer-SiO 2 @NMP under the reaction circumstances.In this investigation, 67% of the product was produced in half the reaction duration (the reaction time is 5 min).The reaction Table 4. Investigating the influence of NMP, bilayer-SiO 2 @NMP, BisPyP@bilayer-SiO 2 @NMP, and Pd-BisPyP@xSiO 2 @NMP in the coupling of iodobenzene with phenylboronic acid as a model compound under optimized conditions.a Isolated yield under optimized conditions.b No reaction.www.nature.com/scientificreports/ was then repeated, and at halftime, the catalyst was separated, and the filtrated solution was allowed to complete the reaction without a catalyst for another 2.5 min.After that, only 69% of biphenyl was recovered as a product.These trials show that palladium leaching did not occur 66 .

Comparison of the catalyst
The efficiency of Pd-BisPyP@bilayer-SiO 2 @NMP as a catalyst was demonstrated by comparing it with the catalysts reported in the literature.Results for the coupling of iodobenzene with phenylboronic acid in the presence of Pd-BisPyP@bilayer-SiO 2 @NMP and previously reported catalysts are summarized in Table 7.In this comparison, various parameters such as reaction condition, reaction times and yields were compared.As shown in Table 7, Pd-BisPyP@bilayer-SiO 2 @NMP showed high effectivity than other catalysts in terms of reaction time and isolated yield.

Conclusions
In this research, we have presented a new organic-metallic nanocatalyst (Pd-BisPyP@bilayer-SiO 2 @NMP) with three unique characteristics, i.e., excellent performance in accelerating the reaction time, magnetic nature, and high porosity.These three properties make this magnetic mesoporous material a versatile and effectual catalyst.The catalytic performance of this catalyst was investigated in Suzuki and Stille cross-coupling reactions.These reactions were carried out in eco-friendly conditions and decorated with the following benefits: high purity of products without generation of side products, simple separation of products and catalyst from each other, the phosphine-free structure of the catalyst, the possibility of recovering and reusing the catalyst up to 6 times, high efficiency under relatively moderate conditions, the use of PEG as a green solvent, and not leaching the catalyst, especially the metal parts (Pd), with the confirmation of hot filtration and ICP-OES methods.The recycling experiment of Pd-BisPyP@bilayer-SiO 2 @NMP in the coupling of iodobenzene with phenylboronic acid (Suzuki reaction).

Table 7 .
Comparison of the activity of Pd-BisPyP@bilayer-SiO 2 @NMP in the reaction of iodobenzene and phenylboronic acid with other catalysts.